Using an insolubilized derivative of prostaglandin E1 (PGE1) prepared by covalently linking PGE1 to omega-amino hexyl agarose matrix (PGE1-hexyl agarose) we have shown that platelet poor plasma previously exposed to the insolubilized hormone is capable of inhibiting ADP or 1-epidephrine induced platelet aggregation. (Science 200, 202, 1978). The results indicate the existence of a cyclic AMP independent pathway for the inhibition of platelet aggregation mediated by PGE1 hexyl agarose through plasma proteins. The summary of the proposed research are: (1) to identify and purify the plasma factor(s) which mediates the inhibition of platelet aggregation induced by the hormone. Identification will be performed using plasma deficient in coagulation factors. Normal plasma will also be fractionated by gel filtration, ion-exchangers and affinity chromatography. (2) To delineate the mechanism of the cyclic AMP independent inhibition of platelet aggregation, the effects of plasma exposed to insolubilized PGE1 on Ca ions uptake and modulation of protein kinase will be assessed. Also, experiments will be performed to determine whether increased levels of cyclic AMP in platelets could increase the synthesis and secretion of PGE1 which in turn might regulate platelet function directly.